Lymphogranuloma venereum (LGV) ompA-subvariants of the Portuguese collection of Chlamydia trachomatis, 2007-2023

Lymphogranuloma venereum (LGV) ompA-subvariants of the Portuguese collection of Chlamydia trachomatis, 2007-2023 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Lymphogranuloma venereum (LGV) ompA-subvariants of the Portuguese collection of Chlamydia trachomatis, 2007-2023 Zohra Lodhia, Dora Cordeiro, Cristina Correia, Ines Joao, Teresa Carreira, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5477659/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Lymphogranuloma venereum is a sexually transmitted infection caused by Chlamydia trachomatis ompA -genotypes L1-L3, with increasing numbers of detected cases across Europe. Here, we analysed diversity and temporal distribution of the LGV ompA -subvariants detected in Portugal between 2007 and 2023, in order to better understand the dissemination and diversification landscape of LGV strains. Methods The collection of the Portuguese National Reference Laboratory includes 1188 LGV ompA -genotyped samples between 2007 and 2023. In-depth analysis of the diversity of LGV ompA -subvariants circulating in Portugal across the years was performed, identifying newly described subvariants and integrating this data in a comprehensive compilation with all representative LGV ompA -subvariants described globally. Results L2 ompA -variant (L2/434/Bu) was consistently the most frequently detected in our collection, with annual proportions ranging from 34.0–82.9%, between 2016 and 2023. L2bV5 was the second most frequent followed by L2b, ranging from 5.0–27.9% and 2.6–23.7% across the years, respectively, from 2017 to 2023. We highlighted the emergence and considerable increase in circulation of L1-like ompA -subvariants in recent years, representing 13.7% of LGV sequences in 2023. We also identified thirteen novel LGV ompA -subvariants that had not been described before, differing by up to three mutations from the respective genotype reference sequences. Conclusions This study contributes for the worldwide picture of the LGV molecular epidemiology, highlighting the importance of long-term molecular surveillance to monitor the circulation and geographical spread of LGV, and timely identify and track new strains, such as the recently emerging L1-like ompA -subvariants. Molecular Epidemiology Sexual & Reproductive Medicine Chlamydia trachomatis Lymphogranuloma venereum ompA-subvariants Figures Figure 1 Figure 2 INTRODUCTION Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by Chlamydia trachomatis ompA -genotypes L1-L3. It is characterised by the dissemination of infection from the genitalia to the inguinal lymph nodes, which typically swell and suppurate [ 1 , 2 ]. Since 2003, outbreaks of LGV have occurred across Europe and other developed countries worldwide, commonly associated with HIV-positive men who have sex with men (MSM) [ 3 – 5 ]. The number of LGV reported cases across Europe increased by 58% from 2021 to 2022, with 2059 cases reported in 2022 by 23 EU/EEA Member States [ 1 ]. Contrary to the classical LGV clinical presentation as inguinal lymphadenopathy, the ongoing LGV epidemic is mainly characterised by the development of proctitis [ 2 , 3 , 6 ], even though it is estimated that approximately 25% of LGV-infected patients remain asymptomatic [ 7 ]. Genome-scale analyses confirmed that the ongoing proctitis-associated LGV epidemic reflects the clonal expansion and global dissemination of a variant of the LGV genotype L2, known as L2b [ 6 , 8 , 9 ]. In most countries with available molecular typing data, this ompA -subvariant has been described as the most prevalent among LGV cases, although other countries, such as Portugal, reported the dominance of the classical “L2” genotype [ 10 – 12 ]. At ompA level, the L2b strain is identified by one single nucleotide polymorphism (SNP) (A/G at position 485) when compared with the ompA -genotype L2 reference sequence (L2/434/Bu strain, accession number AM884176.1) [ 6 ]. Meanwhile, some countries have been reporting the emergence and circulation of other LGV ompA -subvariants with characteristic SNP when compared with L2 (L2/434/Bu) and L2b (L2b/UCH-1) reference strains [ 6 , 13 ], such as the subvariants L2bV1 [ 5 ], L2bV5, L2bV6 [ 14 ] or AM/8/17 [ 15 ]. In addition, a recombinant LGV strain with a hybrid L2-L2b/D-Da ompA sequence has been identified [ 16 ] and found to be circulating worldwide [ 17 ]. This scenario emphasizes the value of the historical ompA -genotyping for tracking circulation and diversification of LGV strains, while reinforcing the need for improved LGV typing techniques for better monitoring the global epidemic [ 18 , 19 ]. The main objective of the present study was to characterise the emergence, diversification, and temporal distribution of LGV ompA -subvariants in Portugal from 2007 and 2023, based on the analysis of the collection of C. trachomatis -positive samples of the National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Lisbon, Portugal. METHODS Sample collection The National Reference Laboratory for Sexually Transmitted Infections (NRL) of INSA, Portugal, is responsible for the collection of C. trachomatis strains and positive specimens. The collection started in 1990, and is composed by viable strains and positive biological samples obtained from the NRL routine laboratory diagnosis activity, as well as by C. trachomatis positive specimens that are routinely and voluntarily sent to the NRL by other Portuguese laboratories, namely three of the major hospitals of the Lisbon area (Unidade Local de Saúde Amadora Sintra, Unidade Local de Saúde Lisboa Ocidental, and Unidade Local de Saúde São José – Centro Clínico Académico de Lisboa). The current NRL collection covers C. trachomatis- positive specimens collected for more than three decades, constituting a valuable basis for monitoring the circulation and diversity of C. trachomatis , as described by Lodhia et al. [ 10 ]. In the present study, we analysed data exclusively from C. trachomatis -positive samples ompA -genotyped as LGV since 2007, encompassing a total of 1188 samples. The database is fully anonymised and, in a systematic manner, only includes the year of detection, biological sex, age, type of specimen, and ompA -genotype. ompA -genotyping and comparative sequence analysis ompA -genotyping of all C. trachomatis -positive samples was performed according to a technique adapted from Lan, et al . [ 20 ], as detailed by Gomes, et al . [ 21 ]. Partial nucleotide sequencing of the ~ 1010bp PCR product was performed with BigDye terminator V.1.1 and capillary sequencing (3130XL Genetic Analyzer; Applied Biosystems), using either two primers, as described elsewhere [ 21 , 22 ], or one primer (since ~ 2018), as described by Borges et al . [ 16 ]. The main ompA -genotypes were classified as described by Borges, et al . [ 10 , 16 ], with LGV including L1, L2, L3 and recombinant L2-L2b/D-Da. The procedure used in this study generated partial ompA sequences, covering the protein Variable Domain (VD) II and thus, the mutation that distinguishes L2/434/Bu and L2b (A485G, located in VDII). In order to classify the LGV ompA -subvariants, all sequences were manually curated and aligned using MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets [ 23 ] against the C. trachomatis prototype-strain L2/434/Bu (National Center for Biotechnology Information (NCBI) accession number AM884176.1), and sequences of LGV ompA -subvariants described in the literature and/or published in the GenBank (Tables 1 and 2 and Supplementary table 1). The alignment was manually curated and inspected to identify all SNPs and insertions/deletions, as well as their impact at protein level, in comparison with L2/434/Bu. Sequences displaying 100% nucleotide identity with representative sequences with previously described LGV ompA -genotypes, and subvariants, were classified as such (Tables 1 and 2 ). Whenever the available ompA region was identical to more than one ompA -subvariant, those were classified as the less divergent subvariant. Sequences with different mutation profile were classified as novel LGV ompA -subvariants, after NCBI BLAST confirmation that they were not previously described. In the absence of an internationally agreed LGV ompA -subvariant nomenclature, the newly described variants were coded according to the LGV ompA -genotype (L2, L2b or recombinant L2-L2b/D-Da), country code (e.g. PT - Portugal) and variant serial number, e.g. L2vPT1. Table 1 – L2 and L2b-like LGV ompA -subvariants, accession numbers, nucleotide and amino acid changes, location of the mutations in the MOMP and source, in comparison to LGV ompA -variant L2/434/Bu (accession number AM884176.1). LGV ompA-subvariant (accession number) Nucleotide change (position) Amino acid change MOMP region Source L2b (AM884177.2) A → G (485) Asn162Ser VDII 10.1101/gr.7020108 L2a (AF304858.1) G → C (471) A → G (480) G → A (496) Syn Syn Ala166Thr Between VDI and VDII; Between VDI and VDII; VDII GenBank 39 (GQ413955.1) A → G (485) C → T (517) Asn162Ser Leu173Phe VDII; VDII 10.3201/eid1611.100379 L2bV1 (JX971936.1) A → G (485) C → A (517) Asn162Ser Leu173Ile VDII; VDII 10.3201/eid2211.160247 L2bV2 (KU518893) A → G (485) A → C (515) Asn162Ser Lys172Thr VDII; VDII 10.3201/eid2211.160247 L2bV3 (KU518894) G → A (286) A → G (485) G → C (994) C → G (995) Ala96Thr Asn162Ser Ala332Arg VDI; VDII; VDIV; VDIV 10.3201/eid2211.160247 L2bV4 (KU518892) A → G (485) C → A (493) Asn162Ser His165Asn VDII; VDII 10.3201/eid2211.160247 L2bV5 (MH253040.1) G → A (271) A → G (485) C → A (493) Ala91Thr Asn162Ser His165Asn VDI; VDII; VDII 10.1136/sextrans-2019-053972 L2bV6 (MH253041.1) A → G (485) G → A (998) Asn162Ser Ser333Asn VDII; VDIV 10.1136/sextrans-2019-053972 L2bV7 (LR882815.1) A → G (485) G → A (998) Asn162Ser Ser333Asn VDII; VDIV 10.1099/mgen.0.000599 L2bV8 (LR882836.1) A → G (485) A → G (997) Asn162Ser Ser333Gly VDII; VDIV 10.1099/mgen.0.000599 L2bV9 (LR882837.1) A → G (485) A → G (997) G → A (998) Asn162Ser Ser333Asp VDII; VDIV; VDIV 10.1099/mgen.0.000599 L2bV10 (LR882771.1) C → A (287) A → G (485) G → A (1000) Ala96Glu Asn162Ser Ala334Thr VDI; VDII; VDIV 10.1099/mgen.0.000599 L2bV11 (LR882858.1) A → G (485) G → A (1000) Asn162Ser Ala334Thr VDII; VDIV 10.1099/mgen.0.000599 L2c (EF460796) A → G (485) C → T (500) Asn162Ser Thr167Ile VDII; VDII 10.1097/OLQ.0b013e31815d6df8 L2d (EF460797.1) C → T (257) A → G (485) Ala86Val Asn162Ser VDI; VDII 10.1097/OLQ.0b013e31815d6df8 L2e (EF460798) C → T (954) Syn VDIV 10.1097/OLQ.0b013e31815d6df8 L2f (EU676181.1) - - - 10.1128/JB.00895-09 L2g (EU676180.1) A → G (485) C → T (517) Asn162Ser Leu173Phe VDII; VDII 10.1128/JB.00895-09 L2h (MH253042.1) A → G (997) Ser333Gly VDIV 10.1136/sextrans-2019-053972 AM/8/17 (MT707652.1) A → G (485) C → A (493) Asn162Ser His165Asn VDII; VDII 10.1136/sextrans-2020-054700 CF/185/18 (MT707653.1) A → G (485) A → G (491) Asn162Ser Asn164Ser VDII; VDII 10.1136/sextrans-2020-054700 L2v1 (LR882813) G → A (496) A → C (515) Ala166Thr Lys172Thr VDII; VDII 10.1099/mgen.0.000599 L2v2 (LR882814) C → T (506) Ser169Leu VDII 10.1099/mgen.0.000599 L2bV12 (M150261JR) A → G (485) A → G (490) Asn162Ser Asn164Asp VDII; VDII 10.3390/microorganisms12030587 L2bV13 (M060890WO) A → G (485) G → A (802) Asn162Ser Asp268Asn VDII; Between VDIII and VDIV 10.3390/microorganisms12030587 L2bV14 (M050195JD) A → G (485) A → G (494) A → C (515) Asn162Ser His165Arg Lys172Thr VDII; VDII; VDII 10.3390/microorganisms12030587 L2i (M170285JP) A → T (485) Asn162Ile VDII 10.3390/microorganisms12030587 L2 variant (PQ151379) G → A (418) Gly140Arg Between VDI and VDII 10.2807/1560–7917.ES.2024.29.19.2300520 L2 variant (PQ151377) G → A (508) G → A (538) Asp170Asn Asp180Asn VDII; VDII 10.2807/1560–7917.ES.2024.29.19.2300520 L2 variant (PQ151378) G → A (489) G → A (512) G → A (622) Syn Ser171Asn Ala208Thr VDII; VDII; Between VDII and VDIII 10.2807/1560–7917.ES.2024.29.19.2300520 L2 variant (PQ151376) T → C (356) G → T (769) Phe119Ser Asp257Tyr Between VDI and VDII; VDIII 10.2807/1560–7917.ES.2024.29.19.2300520 L2b variant (PQ151382) A → G (485) C → T (995) G → A (998) Asn162Ser Ala332Val Ser333Asn VDII; VDIV; VDIV 10.2807/1560–7917.ES.2024.29.19.2300520 L2b variant (PQ151381) A → G (485) G → A (985) G → A (998) Asn162Ser Asp329Asn Ser333Asn VDII; VDIV; VDIV 10.2807/1560–7917.ES.2024.29.19.2300520 L2b variant (PQ151380) A → G (485) C → A (517) G → A (820) Asn162Ser Leu173Ile Ala274Thr VDII; VDII; Between VDIII and VDIV 10.2807/1560–7917.ES.2024.29.19.2300520 L2vPT1 (PQ225209) A → G (494) His165Arg VDII This publication L2vPT2 (PQ318516) C → G (308) Ala103Gly VDI This publication L2bvPT1 (PQ318531) G → A (271) A→ G (485) C → A (493) T → C (690) Ala91Thr Asn162Ser His165Asn Syn VDI; VDII; VDII; Between VDII and VDIII This publication L2bvPT2 (PQ318585) C → G (308) A → G (485) Ala103Gly Asn162Ser VDI; VDII This publication L2bvPT3 (PQ318824) G → A (271) A → G (485) C → A (493) G → A (829) Ala91Thr Asn162Ser His165Ser Ala277Thr VDI; VDII; VDII; Between VDIII and VDIV This publication L2bvPT4 (PQ318895) G → A (271) A → G (485) C → A (493) G → A (624) Ala91Thr Asn162Ser His165Ser Syn VDI; VDII; VDII; Between VDII and VDIII This publication L2vPT3 (PQ319239) G → C (538) G → A (670) Asp180His Glu224Lys VDII; Between VDII and VDIII This publication L2vPT4 (PQ319303) G → A (592) Ala198Thr Between VDII and VDIII This publication L2vPT5 (PQ319308) G → A (634) Ala212Thr Between VDII and VDIII This publication L2vPT6 (PQ319370) G → A (601) Ala201Thr Between VDII and VDIII This publication L2vPT7 (PQ319475) C → T (524) Pro175Leu VDII This publication Recombinant L2-L2b/D-Da (MN094864)* - - - 10.1099/mgen.0.000313 RecL2b/DavPT1 (PQ318779)‡ T→ C (744) Syn VDIII This publication RecL2b/DavPT2 (PQ318842)‡ C → T (690) C → T (891) Syn Syn Between VDII and VDIII; Between VDIII and VDIV This publication VD – Variable Domain; Syn – Synonymous mutation; * Recombinant L2-L2b/D-Da hybrid profile with multiple mutations (see Borges et al , 2019 [ 16 ]); ‡ LGV ompA -subvariants identical to recombinant L2-L2b/D-Da with additional mutations identified in the table in reference to this recombinant. Table 2 – L1-like LGV ompA -subvariants, accession numbers, nucleotide and amino acid changes, location of the mutations in the MOMP and source in comparison to LGV ompA -variant L1/440 (accession number DQ064294.1). LGV ompA-subvariant (accession number) Nucleotide change (position) Amino acid change MOMP region Source 40 (GQ413956.1) G → A (268) T → A (348) C → T (462) G → A (471) A → G (474) C → T (477) C → T (594) C → T (1017) A → C (1020) Ala90Thr Syn Syn Syn Syn Syn Syn Syn Syn VDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDII and VDIII; VDIV; VDIV 10.3201/eid1611.100379 L4 (MN563608) G → A (268) T → A (348) C → T (462) G → A (471) A → G (474) C → T (477) C → T (594) A → G (931) Ala90Thr Syn Syn Syn Syn Syn Syn Thr311Ala VDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDII and VDIII; VDIV 10.3390/microorganisms12030587 L4 with mutation* G → A (268) T → A (348) C → T (462) G → A (471) A → G (474) C → T (477) A → C (507) C → T (594) A → G (931) Ala90Thr Syn Syn Syn Syn Syn Lys169Asn Syn Thr311Ala VDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; VDII; Between VDII and VDIII; VDIV 10.3390/microorganisms12030587 VD – Variable Domain; * Sequence kindly provided by the authors RESULTS LGV samples from the Portuguese collection of C. trachomatis , 2007–2023 Over the course of 17 years (2007–2023), a total of 1188 C. trachomatis -positive samples were ompA -genotyped as LGV at the Portuguese NRL for STI, representing 17.1% (1188/6959) of the INSA C. trachomatis ompA sequence collection in that period (Fig. 1). The most prevalent anatomical site for LGV infections was the anorectum (n = 1082, 91.1%), followed by the urogenital area (n = 78, 6.6%) and the oropharynx (n = 23, 1.9%). For five specimens (0.4%) the anatomical site was unknown (Supplementary table 2). The median age of infected individuals was 34 years (ranging from 16 to 70 years), and the large majority were male (n = 1157, 97.4%). LGV ompA -subvariants The analysis of the 1188 LGV ompA sequences enabled the characterization of C. trachomatis collection into subvariants (Supplementary tables 1 and 2). Between 2007 and 2015, the number of LGV ompA -sequences was very low (less than ten per year), with 54.8% (n = 17) being classified as L2 (i.e., identical to L2/434/Bu; GenBank accession number AM884176.1) [ 6 ] and 38.7% (n = 12) as L2b (i.e., identical to L2b; GenBank accession number AM884177.2) [ 6 , 13 ]. Since 2016, the amount of the LGV ompA -sequences increased substantially (Fig. 1), with the proportion of L2/434/Bu and L2b/UCH-1 matching sequences, per year, ranging between 34.0%-82.9% and 2.6%-23.7% until the end of 2023, respectively (Fig. 1 and Supplementary table 3). Other frequently detected LGV ompA -subvariants included L2bV5 and the recombinant L2-L2b/D-Da, which represented 18.5% (220/1188) and 4.7% (56/1188) of all LGV ompA collection, respectively. L2bV5 was detected in 2017, with the highest proportion (27.9%, n = 50) in 2022. The recombinant L2-L2b/D-Da peaked in our collection in 2018 (15.5%, n = 15), before declining to 3.5% (n = 11) in 2023. Among the other LGV ompA -subvariants detected in the collection, we highlight L2bV1, which represented 2.1% (25/1188) of all LGV sequences and was consistently detected between 2016 and 2023. Apart from the above described L2- and L2b-like ompA -subvariants, we highlight the emergence and considerable circulation of L1 ompA -subvariants in recent years (Table 2 ), namely the subvariant ‘40’, ‘L4’ and ‘L4 with mutation’, which present one and two additional SNPs when comparing to the ‘40’ ompA sequence, respectively [ 24 ]. Subvariant ‘L4 with mutation’ was detected for the first time, in our collection, in 2018 and subvariants ‘40’ and ‘L4’ were both detected in 2022. In 2023, all three L1 ompA -subvariants (i.e., ’40, ‘L4’ and ‘L4 with mutation’) were detected, representing 13.7% of LGV sequences in that year. Less frequently detected LGV ompA -subvariants in Portugal included L2bV2 (0.3%, 3/1188), L2h (0.2%, 2/1188), AM/8/17 (0.2%, 2/1188) and L2g (0.1%, 1/1188), as well as 13 novel LGV ompA -subvariants that had not been described before (Supplementary table 1). The newly identified ompA -subvariants included seven L2-, four L2b- and two recombinant L2-L2b/D-Da-like sequences, which differ by no more than three mutations to the respective genotype reference sequence. All ompA mutations observed across the whole L2-like ompA -subvariants described so far, and analysed here, were scrutinized according to their impact at protein level (Tables 1 and 2 ), with alignment details provided in Supplementary table 4. Most mutations led to amino acid change and fell within the VDs of the antigenic MOMP (Tables 1 and 2 ). No marked differences were observed when analysing the distribution of the LGV ompA -subvariants by anatomical site and biological sex (Fig. 2), with LGV ompA -variant L2/434/Bu being the most frequent across all anatomical sites and biological sexes, followed by L2bV5 and L2b. Despite the low number of samples from females and from the oropharynx, we noted that LGV ompA -subvariant L2bV5 was slightly more frequent in females than in males and that no L2bV1 was detected at the oropharynx. DISCUSSION The increasing burden of LGV in the last decades emphasises the importance of implementing surveillance programs that are able to leverage early diagnosis and treatment, and trace the temporal and geographical spread of LGV strains under circulation [ 1 ]. Within the EU/EEA, Portugal is one of the few countries that maintains an active and long-term (more than three decades) molecular surveillance of C. trachomatis through systematic ompA -genotyping, which has contributed to a deeper understanding of epidemiology, diversity and pathogenicity of this top prevalent sexually transmitted bacterium [ 10 , 16 , 22 ]. The detection of LGV cases in Portugal has considerably increased since 2016, being most frequently identified among anorectal specimens and associated with biological sex, namely being man, despite some cases reported among women [ 10 ]. In the present study, we performed an in-depth assessment of the diversity of LGV ompA -subvariants circulating in Portugal, taking advantage of the 1188 samples that were LGV ompA -genotyped by the Portuguese NRL for STI between 2007–2023, thereby significantly enhancing the worldwide public repository of ompA sequences. Additionally, we gathered sequence data of all representative LGV ompA -subvariants described globally (n = 54) (Supplementary table 1) not only to better integrate the data from Portugal, but also to assemble a comprehensive compilation of subvariants’ nomenclature, representative accession numbers, marker mutations and literature references. Such a systematic compilation has not been previously undertaken, and we anticipate it might serve as a valuable resource for future studies. Upon analysing the LGV ompA -sequences identified in Portugal, it is notable the variety of LGV ompA -subvariants that were detected (24 in total), in tune with other studies [ 12 , 14 , 15 , 19 , 25 ]. Noteworthy, although LGV ompA -subvariant L2b (matching the prototype L2b/UCH-1) has been prevalent among LGV cases in most countries with available molecular typing data [ 13 , 26 ], a shift in the predominance of the L2b ompA -genotyped strains to sequences with ompA matching the L2/434/Bu prototype strain has been described, likely due to the reversion of the ompA A485G mutation in strains with L2b genomic backbone [ 19 ]. An example of this shift was observed in France, in which the predominance of L2b considerably decreased from 75.0–35.0% in 2013, in contrast with prototype L2/434/Bu that increased from 8.3–52.5% in the same years [ 5 , 12 ]. Nonetheless, in Portugal, L2 genotype has been consistently dominant since the onset of the proctitis LGV epidemic, supporting the need for future WGS studies to confirm whether the L2-like ompA -subvariants possess an L2b genomic background with described ompA reversion. The present study also shows that other L2- and L2b-like ompA -subvariants (with 1–3 SNPs in comparison with the respective ompA reference) have been circulating with non-negligible impact on the LGV epidemic, as described in other studies [ 5 , 12 , 14 , 15 , 19 , 24 , 25 ]. For instance, we observed that LGV ompA -subvariant L2bV5, which has a sequence similar to L2b with two additional nucleotide changes in G271A and C493A, conferring non-synonymous mutations (Ala91Thr and His165Asn), was the second most frequent within the Portuguese collection (18.5%), with an overall increased frequency from 5.0% (2017, when it was first detected) to 27.9% (2023). However, in other countries where it has been identified, such as the United Kingdom, Spain or Argentina, the L2bV5 reported proportion has been notably low [ 12 , 19 , 24 ], suggesting that there might be some geographic or population-specific factors contributing to its high prevalence in Portugal. In another perspective, similarly to our previous hypothesis regarding the emergence and transcontinental circulation of the recombinant LGV ompA -subvariant L2-L2b/D-Da [ 16 , 17 ], we cannot exclude that other biological drivers, such as expanded tissue tropism or enhanced transmissibility might justify the differential prevalence of LGV subvariants. Not unexpectedly, we observed that most mutations differentiating the analysed LGV subvariants led to amino acid changes that fall within VDs (and often within epitope regions) of the antigenic MOMP. While speculative, this might reflect ongoing adaptive evolution as VDs, namely VDII, are key antigenic domains of C. trachomatis [ 27 , 28 ] that contain multiple epitopes targeted by the host immune system [ 19 , 22 ]. Recombinant LGV ompA -subvariant L2-L2b/D-Da was very often detected in 2017 and 2018, but has declined in frequency in Portugal, while being reported in multiple countries [ 11 , 12 , 15 , 17 , 19 , 25 ], indicating global dissemination. Nonetheless, considering that many countries have no active molecular surveillance, L2bV5, L2-L2b/D-Da and other subvariants might remain unnoticed; thus, the biological and epidemiological features underlying the success of particular subvariants cannot be currently adequately monitored. Potentiated by the globalization and migration phenomena, this lack of knowledge hampers the early identification of the source of new emergent variants, which are only recognised after broadly dissemination. For instance, since the start of the LGV epidemics in Europe and North America in 2004, L1 ompA -genotypes were rarely reported, namely in the Portuguese collection, until 2021 [ 10 , 29 ]. Still, from that year, its frequency started increasing, representing a remarkable 13.7% proportion of LGV sequences in 2023 in Portugal. L1 ompA -genotypes detected in our collection were either identical to subvariant ‘40’, which was firstly described in San Francisco, USA, back in the 1980s (exhibiting up to 11 point-mutations when compared to the historical L1 prototype strain L1/440 (accession number DQ064294.1) [ 30 ], or identical to ‘L4’ or ‘L4 with mutation’ (differing by one (A931G) or two mutations (A509C and A934G) from the subvariant ‘40’, respectively, as described by Büttner et al . [ 24 ]). In addition to the detection of these profiles in our collection and in Argentina, L1 ompA -subvariants have also been identified in France [ 12 , 24 ], corroborating the hypothesis that epidemiologically and clinically relevant LGV subvariants can (re)emerge and rapidly spread globally without any clues about their source and transmission routes. Rapid tests can currently distinguish between C. trachomatis LGV and non-LGV strains, and the ompA -genotyping procedure usually only generates partial sequences, which do not allow to discriminate additional subvariants. Thus, a rapid procedure to differentiate between L2 and L2b, along with the ability to detect L1 strains, and other frequent LGV subvariants, would be ideal to streamline molecular surveillance efforts. This would contribute to more rapidly track C. trachomatis subvariants emergence and circulation, and to correlate them with specific clinical features towards an enhanced public health response. While multi-loci typing or even WGS would offer an alternative for this issue, these techniques are still costly and laborious options for routine application for an intracellular pathogen like C. trachomatis . In conclusion, the present study comprehends the most extensive and comprehensive evaluation of LGV strains in circulation in Portugal, and provides an important contribution for the worldwide picture of the LGV molecular epidemiology. It highlights the importance of the molecular characterisation of LGV strains and evidences the need for improving LGV screening and long-term monitoring (involving different populations and anatomical sites, as well as in-depth strain characterisation through WGS), which should rationalise surveillance and contribute to implement fittest prevention programs to reduce the burden of LGV epidemics. Declarations Data availability All ompA sequences analysed in this study were submitted to GenBank and accession numbers are provided in Supplementary table 2. The accession numbers of representative sequences of LGV ompA -subvariants addressed in this study, including newly identified subvariants, are listed in Tables 1 and 2 and Supplementary table 1. Data available in supplementary material. ACKNOWLEDGEMENTS: The National Reference Laboratory (NRL) for sexually transmitted infections want to thank: (1) prior members of the staff, as well as to prior students and trainees at NRL that have collaborated in the ompA -genotyping along the years; (2) Maria dos Anjos Catry, PharmD, head of the Chlamydia unit until 2010; (3) Irene Santo, MD, Jacinta Azevedo, MD and Cândida Fernandes, MD, for teaching us so much about sexually transmitted infections and (4) to all laboratories along the country that sporadically send Chlamydia trachomatis -positive specimens to the NRL. Authors contributions: ZL wrote the paper; ZL, VB and MJB analysed the data; SS, EA, CP, IM, EG, SM, APD and RC-R provided samples and data; ZL, DC, CC, IJ, TC, AN, RF, VB, LV, JPG and MJB performed ompA -genotyping. All revised the manuscript. Conflicts of interest: The authors declare that there are no conflicts of interest. 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Published 2024 Mar 15. doi:10.3390/microorganisms12030587. Salmerón P, Serra-Pladevall J, Vall-Mayans M, et al . Genetic characterisation of lymphogranuloma venereum in Spain: a multicentre study. Sex Transm Infect . Published online July 24, 2024. doi:10.1136/sextrans-2023-056021. Stary G, Stary A. Lymphogranuloma venereum outbreak in Europe. J Dtsch Dermatol Ges . 2008;6(11):935-940. doi:10.1111/j.1610-0387.2008.06742.x. Gomes JP, Nunes A, Florindo C, et al . Lymphogranuloma venereum in Portugal: unusual events and new variants during 2007. Sex Transm Dis . 2009;36(2):88-91. doi:10.1097/OLQ.0b013e31818b1e27. Zhong GM, Brunham RC. Antigenic determinants of the chlamydial major outer membrane protein resolved at a single amino acid level. Infect Immun . 1991;59(3):1141-1147. doi:10.1128/iai.59.3.1141-1147.1991. Borrego MJ, Gomes JP, Lefebvre JF, Eb F, Orfila J, Catry MA. Genotyping of Portuguese Chlamydia trachomatis urogenital isolates. Genitourin Med . 1997;73(6):561-563. doi:10.1136/sti.73.6.561. Christerson L, de Vries HJ, de Barbeyrac B, et al . Typing of lymphogranuloma venereum Chlamydia trachomatis strains. Emerg Infect Dis . 2010;16(11):1777-1779. doi:10.3201/eid1611.100379. Additional Declarations The authors declare no competing interests. Supplementary Files Supplementarytable1.xlsx Supplementarytable2.xlsx Supplementarytable3.xlsx Supplementarytable4.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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It is characterised by the dissemination of infection from the genitalia to the inguinal lymph nodes, which typically swell and suppurate [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Since 2003, outbreaks of LGV have occurred across Europe and other developed countries worldwide, commonly associated with HIV-positive men who have sex with men (MSM) [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The number of LGV reported cases across Europe increased by 58% from 2021 to 2022, with 2059 cases reported in 2022 by 23 EU/EEA Member States [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Contrary to the classical LGV clinical presentation as inguinal lymphadenopathy, the ongoing LGV epidemic is mainly characterised by the development of proctitis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], even though it is estimated that approximately 25% of LGV-infected patients remain asymptomatic [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Genome-scale analyses confirmed that the ongoing proctitis-associated LGV epidemic reflects the clonal expansion and global dissemination of a variant of the LGV genotype L2, known as L2b [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In most countries with available molecular typing data, this \u003cem\u003eompA\u003c/em\u003e-subvariant has been described as the most prevalent among LGV cases, although other countries, such as Portugal, reported the dominance of the classical \u0026ldquo;L2\u0026rdquo; genotype [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. At \u003cem\u003eompA\u003c/em\u003e level, the L2b strain is identified by one single nucleotide polymorphism (SNP) (A/G at position 485) when compared with the \u003cem\u003eompA\u003c/em\u003e-genotype L2 reference sequence (L2/434/Bu strain, accession number AM884176.1) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Meanwhile, some countries have been reporting the emergence and circulation of other LGV \u003cem\u003eompA\u003c/em\u003e-subvariants with characteristic SNP when compared with L2 (L2/434/Bu) and L2b (L2b/UCH-1) reference strains [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], such as the subvariants L2bV1 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], L2bV5, L2bV6 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] or AM/8/17 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition, a recombinant LGV strain with a hybrid L2-L2b/D-Da \u003cem\u003eompA\u003c/em\u003e sequence has been identified [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and found to be circulating worldwide [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This scenario emphasizes the value of the historical \u003cem\u003eompA\u003c/em\u003e-genotyping for tracking circulation and diversification of LGV strains, while reinforcing the need for improved LGV typing techniques for better monitoring the global epidemic [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe main objective of the present study was to characterise the emergence, diversification, and temporal distribution of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants in Portugal from 2007 and 2023, based on the analysis of the collection of \u003cem\u003eC. trachomatis\u003c/em\u003e-positive samples of the National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Lisbon, Portugal.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSample collection\u003c/h2\u003e \u003cp\u003eThe National Reference Laboratory for Sexually Transmitted Infections (NRL) of INSA, Portugal, is responsible for the collection of \u003cem\u003eC. trachomatis\u003c/em\u003e strains and positive specimens. The collection started in 1990, and is composed by viable strains and positive biological samples obtained from the NRL routine laboratory diagnosis activity, as well as by \u003cem\u003eC. trachomatis\u003c/em\u003e positive specimens that are routinely and voluntarily sent to the NRL by other Portuguese laboratories, namely three of the major hospitals of the Lisbon area (Unidade Local de Sa\u0026uacute;de Amadora Sintra, Unidade Local de Sa\u0026uacute;de Lisboa Ocidental, and Unidade Local de Sa\u0026uacute;de S\u0026atilde;o Jos\u0026eacute; \u0026ndash; Centro Cl\u0026iacute;nico Acad\u0026eacute;mico de Lisboa). The current NRL collection covers \u003cem\u003eC. trachomatis-\u003c/em\u003epositive specimens collected for more than three decades, constituting a valuable basis for monitoring the circulation and diversity of \u003cem\u003eC. trachomatis\u003c/em\u003e, as described by Lodhia \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In the present study, we analysed data exclusively from \u003cem\u003eC. trachomatis\u003c/em\u003e-positive samples \u003cem\u003eompA\u003c/em\u003e-genotyped as LGV since 2007, encompassing a total of 1188 samples.\u003c/p\u003e \u003cp\u003eThe database is fully anonymised and, in a systematic manner, only includes the year of detection, biological sex, age, type of specimen, and \u003cem\u003eompA\u003c/em\u003e-genotype.\u003c/p\u003e \u003cp\u003e \u003cb\u003eompA\u003c/b\u003e \u003cb\u003e-genotyping and comparative sequence analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eompA\u003c/em\u003e-genotyping of all \u003cem\u003eC. trachomatis\u003c/em\u003e-positive samples was performed according to a technique adapted from Lan, \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], as detailed by Gomes, \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Partial nucleotide sequencing of the ~\u0026thinsp;1010bp PCR product was performed with BigDye terminator V.1.1 and capillary sequencing (3130XL Genetic Analyzer; Applied Biosystems), using either two primers, as described elsewhere [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], or one primer (since ~\u0026thinsp;2018), as described by Borges \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The main \u003cem\u003eompA\u003c/em\u003e-genotypes were classified as described by Borges, \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], with LGV including L1, L2, L3 and recombinant L2-L2b/D-Da. The procedure used in this study generated partial \u003cem\u003eompA\u003c/em\u003e sequences, covering the protein Variable Domain (VD) II and thus, the mutation that distinguishes L2/434/Bu and L2b (A485G, located in VDII). In order to classify the LGV \u003cem\u003eompA\u003c/em\u003e-subvariants, all sequences were manually curated and aligned using MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] against the \u003cem\u003eC. trachomatis\u003c/em\u003e prototype-strain L2/434/Bu (National Center for Biotechnology Information (NCBI) accession number AM884176.1), and sequences of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants described in the literature and/or published in the GenBank (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Supplementary table 1). The alignment was manually curated and inspected to identify all SNPs and insertions/deletions, as well as their impact at protein level, in comparison with L2/434/Bu. Sequences displaying 100% nucleotide identity with representative sequences with previously described LGV \u003cem\u003eompA\u003c/em\u003e-genotypes, and subvariants, were classified as such (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Whenever the available \u003cem\u003eompA\u003c/em\u003e region was identical to more than one \u003cem\u003eompA\u003c/em\u003e-subvariant, those were classified as the less divergent subvariant. Sequences with different mutation profile were classified as novel LGV \u003cem\u003eompA\u003c/em\u003e-subvariants, after NCBI BLAST confirmation that they were not previously described. In the absence of an internationally agreed LGV \u003cem\u003eompA\u003c/em\u003e-subvariant nomenclature, the newly described variants were coded according to the LGV \u003cem\u003eompA\u003c/em\u003e-genotype (L2, L2b or recombinant L2-L2b/D-Da), country code (e.g. PT - Portugal) and variant serial number, e.g. L2vPT1.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; L2 and L2b-like LGV \u003cem\u003eompA\u003c/em\u003e-subvariants, accession numbers, nucleotide and amino acid changes, location of the mutations in the MOMP and source, in comparison to LGV \u003cem\u003eompA\u003c/em\u003e-variant L2/434/Bu (accession number AM884176.1).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLGV ompA-subvariant (accession number)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNucleotide change (position)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAmino acid change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMOMP region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2b\u003c/p\u003e \u003cp\u003e(AM884177.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1101/gr.7020108\u003c/span\u003e\u003cspan address=\"10.1101/gr.7020108\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2a\u003c/p\u003e \u003cp\u003e(AF304858.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; C (471)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (480)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (496)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eAla166Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDI and VDII; Between VDI and VDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGenBank\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003cp\u003e(GQ413955.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (517)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eLeu173Phe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid1611.100379\u003c/span\u003e\u003cspan address=\"10.3201/eid1611.100379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV1\u003c/p\u003e \u003cp\u003e(JX971936.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (517)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eLeu173Ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid2211.160247\u003c/span\u003e\u003cspan address=\"10.3201/eid2211.160247\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV2\u003c/p\u003e \u003cp\u003e(KU518893)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; C (515)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eLys172Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid2211.160247\u003c/span\u003e\u003cspan address=\"10.3201/eid2211.160247\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV3\u003c/p\u003e \u003cp\u003e(KU518894)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (286)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; C (994)\u003c/p\u003e \u003cp\u003eC \u0026rarr; G (995)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla96Thr\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAla332Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII; VDIV; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid2211.160247\u003c/span\u003e\u003cspan address=\"10.3201/eid2211.160247\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV4\u003c/p\u003e \u003cp\u003e(KU518892)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid2211.160247\u003c/span\u003e\u003cspan address=\"10.3201/eid2211.160247\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV5\u003c/p\u003e \u003cp\u003e(MH253040.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (271)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla91Thr\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/sextrans-2019-053972\u003c/span\u003e\u003cspan address=\"10.1136/sextrans-2019-053972\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV6\u003c/p\u003e \u003cp\u003e(MH253041.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eSer333Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/sextrans-2019-053972\u003c/span\u003e\u003cspan address=\"10.1136/sextrans-2019-053972\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV7\u003c/p\u003e \u003cp\u003e(LR882815.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eSer333Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV8\u003c/p\u003e \u003cp\u003e(LR882836.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (997)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eSer333Gly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV9\u003c/p\u003e \u003cp\u003e(LR882837.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (997)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eSer333Asp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV10\u003c/p\u003e \u003cp\u003e(LR882771.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; A (287)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (1000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla96Glu\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAla334Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV11\u003c/p\u003e \u003cp\u003e(LR882858.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (1000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAla334Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2c\u003c/p\u003e \u003cp\u003e(EF460796)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (500)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eThr167Ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0b013e31815d6df8\u003c/span\u003e\u003cspan address=\"10.1097/OLQ.0b013e31815d6df8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2d\u003c/p\u003e \u003cp\u003e(EF460797.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; T (257)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla86Val\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0b013e31815d6df8\u003c/span\u003e\u003cspan address=\"10.1097/OLQ.0b013e31815d6df8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2e\u003c/p\u003e \u003cp\u003e(EF460798)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; T (954)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0b013e31815d6df8\u003c/span\u003e\u003cspan address=\"10.1097/OLQ.0b013e31815d6df8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2f\u003c/p\u003e \u003cp\u003e(EU676181.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/JB.00895-09\u003c/span\u003e\u003cspan address=\"10.1128/JB.00895-09\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2g\u003c/p\u003e \u003cp\u003e(EU676180.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (517)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eLeu173Phe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/JB.00895-09\u003c/span\u003e\u003cspan address=\"10.1128/JB.00895-09\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2h\u003c/p\u003e \u003cp\u003e(MH253042.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (997)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSer333Gly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/sextrans-2019-053972\u003c/span\u003e\u003cspan address=\"10.1136/sextrans-2019-053972\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAM/8/17\u003c/p\u003e \u003cp\u003e(MT707652.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/sextrans-2020-054700\u003c/span\u003e\u003cspan address=\"10.1136/sextrans-2020-054700\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCF/185/18\u003c/p\u003e \u003cp\u003e(MT707653.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (491)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAsn164Ser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/sextrans-2020-054700\u003c/span\u003e\u003cspan address=\"10.1136/sextrans-2020-054700\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2v1\u003c/p\u003e \u003cp\u003e(LR882813)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (496)\u003c/p\u003e \u003cp\u003eA \u0026rarr; C (515)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla166Thr\u003c/p\u003e \u003cp\u003eLys172Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2v2\u003c/p\u003e \u003cp\u003e(LR882814)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; T (506)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSer169Leu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000599\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000599\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV12\u003c/p\u003e \u003cp\u003e(M150261JR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (490)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAsn164Asp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV13\u003c/p\u003e \u003cp\u003e(M060890WO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (802)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAsp268Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; Between VDIII and VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bV14\u003c/p\u003e \u003cp\u003e(M050195JD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (494)\u003c/p\u003e \u003cp\u003eA \u0026rarr; C (515)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Arg\u003c/p\u003e \u003cp\u003eLys172Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2i\u003c/p\u003e \u003cp\u003e(M170285JP)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; T (485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2 variant\u003c/p\u003e \u003cp\u003e(PQ151379)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (418)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGly140Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDI and VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2 variant\u003c/p\u003e \u003cp\u003e(PQ151377)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (508)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (538)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsp170Asn\u003c/p\u003e \u003cp\u003eAsp180Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2 variant\u003c/p\u003e \u003cp\u003e(PQ151378)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (489)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (512)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (622)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSer171Asn\u003c/p\u003e \u003cp\u003eAla208Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII; Between VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2 variant\u003c/p\u003e \u003cp\u003e(PQ151376)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT \u0026rarr; C (356)\u003c/p\u003e \u003cp\u003eG \u0026rarr; T (769)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePhe119Ser\u003c/p\u003e \u003cp\u003eAsp257Tyr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDI and VDII; VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2b variant\u003c/p\u003e \u003cp\u003e(PQ151382)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (995)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAla332Val\u003c/p\u003e \u003cp\u003eSer333Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2b variant\u003c/p\u003e \u003cp\u003e(PQ151381)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (985)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (998)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eAsp329Asn\u003c/p\u003e \u003cp\u003eSer333Asn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDIV; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2b variant\u003c/p\u003e \u003cp\u003e(PQ151380)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (517)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (820)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eLeu173Ile\u003c/p\u003e \u003cp\u003eAla274Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; VDII; Between VDIII and VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\u003c/span\u003e\u003cspan address=\"10.2807/1560\u0026ndash;7917.ES.2024.29.19.2300520\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT1\u003c/p\u003e \u003cp\u003e(PQ225209)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA \u0026rarr; G (494)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHis165Arg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT2\u003c/p\u003e \u003cp\u003e(PQ318516)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; G (308)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla103Gly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bvPT1\u003c/p\u003e \u003cp\u003e(PQ318531)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (271)\u003c/p\u003e \u003cp\u003eA\u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003cp\u003eT \u0026rarr; C (690)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla91Thr\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Asn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII; VDII;\u003c/p\u003e \u003cp\u003eBetween VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bvPT2\u003c/p\u003e \u003cp\u003e(PQ318585)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; G (308)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla103Gly\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bvPT3\u003c/p\u003e \u003cp\u003e(PQ318824)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (271)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (829)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla91Thr\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Ser\u003c/p\u003e \u003cp\u003eAla277Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDI; VDII; VDII; Between VDIII and VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2bvPT4\u003c/p\u003e \u003cp\u003e(PQ318895)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (271)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (485)\u003c/p\u003e \u003cp\u003eC \u0026rarr; A (493)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (624)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAla91Thr\u003c/p\u003e \u003cp\u003eAsn162Ser\u003c/p\u003e \u003cp\u003eHis165Ser\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVDI; VDII; VDII; Between VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT3\u003c/p\u003e \u003cp\u003e(PQ319239)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; C (538)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (670)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsp180His\u003c/p\u003e \u003cp\u003eGlu224Lys\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII; Between VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT4\u003c/p\u003e \u003cp\u003e(PQ319303)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (592)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla198Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT5\u003c/p\u003e \u003cp\u003e(PQ319308)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (634)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla212Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT6\u003c/p\u003e \u003cp\u003e(PQ319370)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (601)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla201Thr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDII and VDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL2vPT7\u003c/p\u003e \u003cp\u003e(PQ319475)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; T (524)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePro175Leu\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecombinant L2-L2b/D-Da\u003c/p\u003e \u003cp\u003e(MN094864)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/mgen.0.000313\u003c/span\u003e\u003cspan address=\"10.1099/mgen.0.000313\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecL2b/DavPT1\u003c/p\u003e \u003cp\u003e(PQ318779)\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT\u0026rarr; C (744)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eVDIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecL2b/DavPT2\u003c/p\u003e \u003cp\u003e(PQ318842)\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC \u0026rarr; T (690)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (891)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBetween VDII and VDIII; Between VDIII and VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eThis publication\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cb\u003eVD\u003c/b\u003e \u0026ndash; Variable Domain; \u003cb\u003eSyn\u003c/b\u003e \u0026ndash; Synonymous mutation; \u003cb\u003e*\u003c/b\u003e Recombinant L2-L2b/D-Da hybrid profile with multiple mutations (see Borges \u003cem\u003eet al\u003c/em\u003e, 2019 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]); \u003cb\u003e\u0026Dagger;\u003c/b\u003e LGV \u003cem\u003eompA\u003c/em\u003e-subvariants identical to recombinant L2-L2b/D-Da with additional mutations identified in the table in reference to this recombinant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; L1-like LGV \u003cem\u003eompA\u003c/em\u003e-subvariants, accession numbers, nucleotide and amino acid changes, location of the mutations in the MOMP and source in comparison to LGV \u003cem\u003eompA\u003c/em\u003e-variant L1/440 (accession number DQ064294.1).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLGV ompA-subvariant (accession number)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNucleotide change (position)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAmino acid change\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMOMP region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSource\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003cp\u003e(GQ413956.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (268)\u003c/p\u003e \u003cp\u003eT \u0026rarr; A (348)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (462)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (471)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (474)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (477)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (594)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (1017)\u003c/p\u003e \u003cp\u003eA \u0026rarr; C (1020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla90Thr\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDII and VDIII; VDIV; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3201/eid1611.100379\u003c/span\u003e\u003cspan address=\"10.3201/eid1611.100379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL4\u003c/p\u003e \u003cp\u003e(MN563608)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (268)\u003c/p\u003e \u003cp\u003eT \u0026rarr; A (348)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (462)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (471)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (474)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (477)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (594)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (931)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla90Thr\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eThr311Ala\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDII and VDIII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eL4 with mutation*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eG \u0026rarr; A (268)\u003c/p\u003e \u003cp\u003eT \u0026rarr; A (348)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (462)\u003c/p\u003e \u003cp\u003eG \u0026rarr; A (471)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (474)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (477)\u003c/p\u003e \u003cp\u003eA \u0026rarr; C (507)\u003c/p\u003e \u003cp\u003eC \u0026rarr; T (594)\u003c/p\u003e \u003cp\u003eA \u0026rarr; G (931)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAla90Thr\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eLys169Asn\u003c/p\u003e \u003cp\u003eSyn\u003c/p\u003e \u003cp\u003eThr311Ala\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVDI; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; Between VDI and VDII; VDII; Between VDII and VDIII; VDIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/microorganisms12030587\u003c/span\u003e\u003cspan address=\"10.3390/microorganisms12030587\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eVD \u0026ndash; Variable Domain; * Sequence kindly provided by the authors\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cb\u003eLGV samples from the Portuguese collection of\u003c/b\u003e \u003cb\u003eC. trachomatis\u003c/b\u003e, \u003cb\u003e2007\u0026ndash;2023\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOver the course of 17 years (2007\u0026ndash;2023), a total of 1188 \u003cem\u003eC. trachomatis\u003c/em\u003e-positive samples were \u003cem\u003eompA\u003c/em\u003e-genotyped as LGV at the Portuguese NRL for STI, representing 17.1% (1188/6959) of the INSA \u003cem\u003eC. trachomatis ompA\u003c/em\u003e sequence collection in that period (Fig.\u0026nbsp;1). The most prevalent anatomical site for LGV infections was the anorectum (n\u0026thinsp;=\u0026thinsp;1082, 91.1%), followed by the urogenital area (n\u0026thinsp;=\u0026thinsp;78, 6.6%) and the oropharynx (n\u0026thinsp;=\u0026thinsp;23, 1.9%). For five specimens (0.4%) the anatomical site was unknown (Supplementary table 2). The median age of infected individuals was 34 years (ranging from 16 to 70 years), and the large majority were male (n\u0026thinsp;=\u0026thinsp;1157, 97.4%).\u003c/p\u003e \u003cp\u003e \u003cb\u003eLGV\u003c/b\u003e \u003cb\u003eompA\u003c/b\u003e\u003cb\u003e-subvariants\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe analysis of the 1188 LGV \u003cem\u003eompA\u003c/em\u003e sequences enabled the characterization of \u003cem\u003eC. trachomatis\u003c/em\u003e collection into subvariants (Supplementary tables 1 and 2). Between 2007 and 2015, the number of LGV \u003cem\u003eompA\u003c/em\u003e-sequences was very low (less than ten \u003cem\u003eper\u003c/em\u003e year), with 54.8% (n\u0026thinsp;=\u0026thinsp;17) being classified as L2 (i.e., identical to L2/434/Bu; GenBank accession number AM884176.1) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and 38.7% (n\u0026thinsp;=\u0026thinsp;12) as L2b (i.e., identical to L2b; GenBank accession number AM884177.2) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Since 2016, the amount of the LGV \u003cem\u003eompA\u003c/em\u003e-sequences increased substantially (Fig.\u0026nbsp;1), with the proportion of L2/434/Bu and L2b/UCH-1 matching sequences, \u003cem\u003eper\u003c/em\u003e year, ranging between 34.0%-82.9% and 2.6%-23.7% until the end of 2023, respectively (Fig.\u0026nbsp;1 and Supplementary table 3). Other frequently detected LGV \u003cem\u003eompA\u003c/em\u003e-subvariants included L2bV5 and the recombinant L2-L2b/D-Da, which represented 18.5% (220/1188) and 4.7% (56/1188) of all LGV \u003cem\u003eompA\u003c/em\u003e collection, respectively. L2bV5 was detected in 2017, with the highest proportion (27.9%, n\u0026thinsp;=\u0026thinsp;50) in 2022. The recombinant L2-L2b/D-Da peaked in our collection in 2018 (15.5%, n\u0026thinsp;=\u0026thinsp;15), before declining to 3.5% (n\u0026thinsp;=\u0026thinsp;11) in 2023. Among the other LGV \u003cem\u003eompA\u003c/em\u003e-subvariants detected in the collection, we highlight L2bV1, which represented 2.1% (25/1188) of all LGV sequences and was consistently detected between 2016 and 2023. Apart from the above described L2- and L2b-like \u003cem\u003eompA\u003c/em\u003e-subvariants, we highlight the emergence and considerable circulation of L1 \u003cem\u003eompA\u003c/em\u003e-subvariants in recent years (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), namely the subvariant \u0026lsquo;40\u0026rsquo;, \u0026lsquo;L4\u0026rsquo; and \u0026lsquo;L4 with mutation\u0026rsquo;, which present one and two additional SNPs when comparing to the \u0026lsquo;40\u0026rsquo; \u003cem\u003eompA\u003c/em\u003e sequence, respectively [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Subvariant \u0026lsquo;L4 with mutation\u0026rsquo; was detected for the first time, in our collection, in 2018 and subvariants \u0026lsquo;40\u0026rsquo; and \u0026lsquo;L4\u0026rsquo; were both detected in 2022. In 2023, all three L1 \u003cem\u003eompA\u003c/em\u003e-subvariants (i.e., \u0026rsquo;40, \u0026lsquo;L4\u0026rsquo; and \u0026lsquo;L4 with mutation\u0026rsquo;) were detected, representing 13.7% of LGV sequences in that year.\u003c/p\u003e \u003cp\u003eLess frequently detected LGV \u003cem\u003eompA\u003c/em\u003e-subvariants in Portugal included L2bV2 (0.3%, 3/1188), L2h (0.2%, 2/1188), AM/8/17 (0.2%, 2/1188) and L2g (0.1%, 1/1188), as well as 13 novel LGV \u003cem\u003eompA\u003c/em\u003e-subvariants that had not been described before (Supplementary table 1). The newly identified \u003cem\u003eompA\u003c/em\u003e-subvariants included seven L2-, four L2b- and two recombinant L2-L2b/D-Da-like sequences, which differ by no more than three mutations to the respective genotype reference sequence.\u003c/p\u003e \u003cp\u003eAll \u003cem\u003eompA\u003c/em\u003e mutations observed across the whole L2-like \u003cem\u003eompA\u003c/em\u003e-subvariants described so far, and analysed here, were scrutinized according to their impact at protein level (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), with alignment details provided in Supplementary table 4. Most mutations led to amino acid change and fell within the VDs of the antigenic MOMP (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNo marked differences were observed when analysing the distribution of the LGV \u003cem\u003eompA\u003c/em\u003e-subvariants by anatomical site and biological sex (Fig.\u0026nbsp;2), with LGV \u003cem\u003eompA\u003c/em\u003e-variant L2/434/Bu being the most frequent across all anatomical sites and biological sexes, followed by L2bV5 and L2b. Despite the low number of samples from females and from the oropharynx, we noted that LGV \u003cem\u003eompA\u003c/em\u003e-subvariant L2bV5 was slightly more frequent in females than in males and that no L2bV1 was detected at the oropharynx.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe increasing burden of LGV in the last decades emphasises the importance of implementing surveillance programs that are able to leverage early diagnosis and treatment, and trace the temporal and geographical spread of LGV strains under circulation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Within the EU/EEA, Portugal is one of the few countries that maintains an active and long-term (more than three decades) molecular surveillance of \u003cem\u003eC. trachomatis\u003c/em\u003e through systematic \u003cem\u003eompA\u003c/em\u003e-genotyping, which has contributed to a deeper understanding of epidemiology, diversity and pathogenicity of this top prevalent sexually transmitted bacterium [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The detection of LGV cases in Portugal has considerably increased since 2016, being most frequently identified among anorectal specimens and associated with biological sex, namely being man, despite some cases reported among women [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present study, we performed an in-depth assessment of the diversity of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants circulating in Portugal, taking advantage of the 1188 samples that were LGV \u003cem\u003eompA\u003c/em\u003e-genotyped by the Portuguese NRL for STI between 2007\u0026ndash;2023, thereby significantly enhancing the worldwide public repository of \u003cem\u003eompA\u003c/em\u003e sequences. Additionally, we gathered sequence data of all representative LGV \u003cem\u003eompA\u003c/em\u003e-subvariants described globally (n\u0026thinsp;=\u0026thinsp;54) (Supplementary table 1) not only to better integrate the data from Portugal, but also to assemble a comprehensive compilation of subvariants\u0026rsquo; nomenclature, representative accession numbers, marker mutations and literature references. Such a systematic compilation has not been previously undertaken, and we anticipate it might serve as a valuable resource for future studies.\u003c/p\u003e \u003cp\u003eUpon analysing the LGV \u003cem\u003eompA\u003c/em\u003e-sequences identified in Portugal, it is notable the variety of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants that were detected (24 in total), in tune with other studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Noteworthy, although LGV \u003cem\u003eompA\u003c/em\u003e-subvariant L2b (matching the prototype L2b/UCH-1) has been prevalent among LGV cases in most countries with available molecular typing data [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], a shift in the predominance of the L2b \u003cem\u003eompA\u003c/em\u003e-genotyped strains to sequences with \u003cem\u003eompA\u003c/em\u003e matching the L2/434/Bu prototype strain has been described, likely due to the reversion of the \u003cem\u003eompA\u003c/em\u003e A485G mutation in strains with L2b genomic backbone [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. An example of this shift was observed in France, in which the predominance of L2b considerably decreased from 75.0\u0026ndash;35.0% in 2013, in contrast with prototype L2/434/Bu that increased from 8.3\u0026ndash;52.5% in the same years [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Nonetheless, in Portugal, L2 genotype has been consistently dominant since the onset of the proctitis LGV epidemic, supporting the need for future WGS studies to confirm whether the L2-like \u003cem\u003eompA\u003c/em\u003e-subvariants possess an L2b genomic background with described \u003cem\u003eompA\u003c/em\u003e reversion. The present study also shows that other L2- and L2b-like \u003cem\u003eompA\u003c/em\u003e-subvariants (with 1\u0026ndash;3 SNPs in comparison with the respective \u003cem\u003eompA\u003c/em\u003e reference) have been circulating with non-negligible impact on the LGV epidemic, as described in other studies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. For instance, we observed that LGV \u003cem\u003eompA\u003c/em\u003e-subvariant L2bV5, which has a sequence similar to L2b with two additional nucleotide changes in G271A and C493A, conferring non-synonymous mutations (Ala91Thr and His165Asn), was the second most frequent within the Portuguese collection (18.5%), with an overall increased frequency from 5.0% (2017, when it was first detected) to 27.9% (2023). However, in other countries where it has been identified, such as the United Kingdom, Spain or Argentina, the L2bV5 reported proportion has been notably low [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], suggesting that there might be some geographic or population-specific factors contributing to its high prevalence in Portugal. In another perspective, similarly to our previous hypothesis regarding the emergence and transcontinental circulation of the recombinant LGV \u003cem\u003eompA\u003c/em\u003e-subvariant L2-L2b/D-Da [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], we cannot exclude that other biological drivers, such as expanded tissue tropism or enhanced transmissibility might justify the differential prevalence of LGV subvariants. Not unexpectedly, we observed that most mutations differentiating the analysed LGV subvariants led to amino acid changes that fall within VDs (and often within epitope regions) of the antigenic MOMP. While speculative, this might reflect ongoing adaptive evolution as VDs, namely VDII, are key antigenic domains of \u003cem\u003eC. trachomatis\u003c/em\u003e [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] that contain multiple epitopes targeted by the host immune system [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecombinant LGV \u003cem\u003eompA\u003c/em\u003e-subvariant L2-L2b/D-Da was very often detected in 2017 and 2018, but has declined in frequency in Portugal, while being reported in multiple countries [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], indicating global dissemination. Nonetheless, considering that many countries have no active molecular surveillance, L2bV5, L2-L2b/D-Da and other subvariants might remain unnoticed; thus, the biological and epidemiological features underlying the success of particular subvariants cannot be currently adequately monitored. Potentiated by the globalization and migration phenomena, this lack of knowledge hampers the early identification of the source of new emergent variants, which are only recognised after broadly dissemination. For instance, since the start of the LGV epidemics in Europe and North America in 2004, L1 \u003cem\u003eompA\u003c/em\u003e-genotypes were rarely reported, namely in the Portuguese collection, until 2021 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Still, from that year, its frequency started increasing, representing a remarkable 13.7% proportion of LGV sequences in 2023 in Portugal. L1 \u003cem\u003eompA\u003c/em\u003e-genotypes detected in our collection were either identical to subvariant \u0026lsquo;40\u0026rsquo;, which was firstly described in San Francisco, USA, back in the 1980s (exhibiting up to 11 point-mutations when compared to the historical L1 prototype strain L1/440 (accession number DQ064294.1) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], or identical to \u0026lsquo;L4\u0026rsquo; or \u0026lsquo;L4 with mutation\u0026rsquo; (differing by one (A931G) or two mutations (A509C and A934G) from the subvariant \u0026lsquo;40\u0026rsquo;, respectively, as described by B\u0026uuml;ttner \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]). In addition to the detection of these profiles in our collection and in Argentina, L1 \u003cem\u003eompA\u003c/em\u003e-subvariants have also been identified in France [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], corroborating the hypothesis that epidemiologically and clinically relevant LGV subvariants can (re)emerge and rapidly spread globally without any clues about their source and transmission routes.\u003c/p\u003e \u003cp\u003eRapid tests can currently distinguish between \u003cem\u003eC. trachomatis\u003c/em\u003e LGV and non-LGV strains, and the \u003cem\u003eompA\u003c/em\u003e-genotyping procedure usually only generates partial sequences, which do not allow to discriminate additional subvariants. Thus, a rapid procedure to differentiate between L2 and L2b, along with the ability to detect L1 strains, and other frequent LGV subvariants, would be ideal to streamline molecular surveillance efforts. This would contribute to more rapidly track \u003cem\u003eC. trachomatis\u003c/em\u003e subvariants emergence and circulation, and to correlate them with specific clinical features towards an enhanced public health response. While multi-loci typing or even WGS would offer an alternative for this issue, these techniques are still costly and laborious options for routine application for an intracellular pathogen like \u003cem\u003eC. trachomatis\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eIn conclusion, the present study comprehends the most extensive and comprehensive evaluation of LGV strains in circulation in Portugal, and provides an important contribution for the worldwide picture of the LGV molecular epidemiology. It highlights the importance of the molecular characterisation of LGV strains and evidences the need for improving LGV screening and long-term monitoring (involving different populations and anatomical sites, as well as in-depth strain characterisation through WGS), which should rationalise surveillance and contribute to implement fittest prevention programs to reduce the burden of LGV epidemics.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll \u003cem\u003eompA\u003c/em\u003e sequences analysed in this study were submitted to GenBank and accession numbers are provided in Supplementary table 2. The accession numbers of representative sequences of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants addressed in this study, including newly identified subvariants, are listed in Tables 1 and 2 and Supplementary table 1.\u0026nbsp;\u003cem\u003eData available in supplementary material.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS:\u003c/strong\u003e The National Reference Laboratory (NRL) for sexually transmitted infections want to thank: (1) prior members of the staff, as well as to prior students and trainees at NRL that have collaborated in the \u003cem\u003eompA\u003c/em\u003e-genotyping along the years; (2) Maria dos Anjos Catry, PharmD, head of the \u003cem\u003eChlamydia\u003c/em\u003e unit until 2010; (3) Irene Santo, MD, Jacinta Azevedo, MD and Cândida Fernandes, MD, for teaching us so much about sexually transmitted infections and (4) to all laboratories along the country that sporadically send \u003cem\u003eChlamydia trachomatis\u003c/em\u003e-positive specimens to the NRL.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions:\u003c/strong\u003e ZL wrote the paper; ZL, VB and MJB analysed the data; SS, EA, CP, IM, EG, SM, APD and RC-R provided samples and data; ZL, DC, CC, IJ, TC, AN, RF, VB, LV, JPG and MJB performed \u003cem\u003eompA\u003c/em\u003e-genotyping. All revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e The authors declare that there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information:\u003c/strong\u003e The authors received no specific grant from any funding agency.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eEuropean Centre for Disease Prevention and Control. Lymphogranuloma venereum. In: ECDC. Annual Epidemiological Report for 2022. Stockholm: ECDC; 2024.\u003c/li\u003e\n\u003cli\u003eSavage EJ, van de Laar MJ, Gallay A, \u003cem\u003eet al\u003c/em\u003e. Lymphogranuloma venereum in Europe, 2003-2008. \u003cem\u003eEuro Surveill\u003c/em\u003e. 2009;14(48):19428. 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Genotyping of Portuguese \u003cem\u003eChlamydia trachomatis\u003c/em\u003e urogenital isolates. \u003cem\u003eGenitourin Med\u003c/em\u003e. 1997;73(6):561-563. doi:10.1136/sti.73.6.561.\u003c/li\u003e\n\u003cli\u003eChristerson L, de Vries HJ, de Barbeyrac B, \u003cem\u003eet al\u003c/em\u003e. Typing of lymphogranuloma venereum \u003cem\u003eChlamydia trachomatis\u003c/em\u003e strains. \u003cem\u003eEmerg Infect Dis\u003c/em\u003e. 2010;16(11):1777-1779. doi:10.3201/eid1611.100379.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"National Institute of Health Doutor Ricardo Jorge","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Chlamydia trachomatis, Lymphogranuloma venereum, ompA-subvariants","lastPublishedDoi":"10.21203/rs.3.rs-5477659/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5477659/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eLymphogranuloma venereum is a sexually transmitted infection caused by \u003cem\u003eChlamydia trachomatis ompA\u003c/em\u003e-genotypes L1-L3, with increasing numbers of detected cases across Europe. Here, we analysed diversity and temporal distribution of the LGV \u003cem\u003eompA\u003c/em\u003e-subvariants detected in Portugal between 2007 and 2023, in order to better understand the dissemination and diversification landscape of LGV strains.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe collection of the Portuguese National Reference Laboratory includes 1188 LGV \u003cem\u003eompA\u003c/em\u003e-genotyped samples between 2007 and 2023. In-depth analysis of the diversity of LGV \u003cem\u003eompA\u003c/em\u003e-subvariants circulating in Portugal across the years was performed, identifying newly described subvariants and integrating this data in a comprehensive compilation with all representative LGV \u003cem\u003eompA\u003c/em\u003e-subvariants described globally.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eL2 \u003cem\u003eompA\u003c/em\u003e-variant (L2/434/Bu) was consistently the most frequently detected in our collection, with annual proportions ranging from 34.0\u0026ndash;82.9%, between 2016 and 2023. L2bV5 was the second most frequent followed by L2b, ranging from 5.0\u0026ndash;27.9% and 2.6\u0026ndash;23.7% across the years, respectively, from 2017 to 2023. We highlighted the emergence and considerable increase in circulation of L1-like \u003cem\u003eompA\u003c/em\u003e-subvariants in recent years, representing 13.7% of LGV sequences in 2023. We also identified thirteen novel LGV \u003cem\u003eompA\u003c/em\u003e-subvariants that had not been described before, differing by up to three mutations from the respective genotype reference sequences.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study contributes for the worldwide picture of the LGV molecular epidemiology, highlighting the importance of long-term molecular surveillance to monitor the circulation and geographical spread of LGV, and timely identify and track new strains, such as the recently emerging L1-like \u003cem\u003eompA\u003c/em\u003e-subvariants.\u003c/p\u003e","manuscriptTitle":"Lymphogranuloma venereum (LGV) ompA-subvariants of the Portuguese collection of Chlamydia trachomatis, 2007-2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 14:28:30","doi":"10.21203/rs.3.rs-5477659/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1466d38f-8871-4379-b539-80767c918ac8","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":40437498,"name":"Molecular Epidemiology"},{"id":40437499,"name":"Sexual \u0026 Reproductive Medicine"}],"tags":[],"updatedAt":"2024-11-19T14:28:30+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 14:28:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5477659","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5477659","identity":"rs-5477659","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}